Pig Lymphocytes Utilise Mouse MAdCAM-1 to Enter Fetal Gut Xenografts in SCID Mice

Ileocecal junction (ICJ) and proximal intestine (PI) fragments from CD45323−allovariant fetal pigs were grafted subcutaneously into SCID mice. The xenografts were examined 8–12 weeks later using two-color immunohistology and the ICJ, but not PI, xenografts were found to contain three types of vessels. The first (the majority) was lined with mouse endothelium (mAb 9F1+), the second was lined with pig endothelium, and the third was chimeric. The ICJ vessels were specifically lined with mouse endothelium expressing MAdCAM-1, the mucosal addressin. Vessels lined with pig endothelium alone did not express the MAdCAM-1 epitopes. Radiolabeled allovariant pig peripheral blood lymphocytes (PBL) were introduced i.v. into the xenografted SCID mice, and entry into xenografts studied. Pig PBL were occasionally seen in MECA-367+vessel walls after 4 h and within the ICJ but not PI xenografts after 24 h. This entry was specifically blocked by coinjection of the anti-MAdCAM-1 mAb MECA-367. The results demonstrate reendothelialization of xenografts by host endothelium that expresses its own addressin and is functional for xenogenic PBL.